THE RANDOMISED CONTROLLED TRIAL has been the gold standard of clinical evidence for more than seventy years. Its logic is elegant: by randomly assigning patients to treatment and control groups, it controls for confounding variables and generates evidence that can, in principle, be attributed to the intervention rather than to any other factor. This logic has served pharmaceutical regulation extraordinarily well, providing the evidentiary basis for thousands of drug approvals and protecting billions of patients from harms that might otherwise have remained invisible. It has also produced a profound limitation: randomised controlled trials are expensive, slow, selective about which patients they enrol, and designed to detect average treatment effects across populations — not the heterogeneous patterns of response and adverse reaction that characterise real clinical practice. The era of pervasive digital health, wearables, and electronic health records is now providing the evidentiary infrastructure to fundamentally expand what counts as acceptable evidence in pharmaceutical regulation.
Real-World Evidence (RWE) — clinical evidence derived from the analysis of Real-World Data (RWD) gathered outside the controlled trial setting — is not a new concept. Its use in post-market surveillance, pharmacovigilance, and observational epidemiology has a long history. What is new is the regulatory willingness to accept RWE as primary evidence in support of drug and device approvals, expanded indications, and safety labelling changes. The pivotal development arrived on 15 December 2025, when the FDA announced that it was eliminating a major barrier to RWE use by allowing de-identified and aggregate data sources — without requiring sponsors to submit individually identifiable patient-level records — in regulatory submissions for medical devices, with explicit signalling that parallel changes for drugs and biologics would follow.
The FDA’s December 2025 Guidance
The FDA’s final guidance on ‘Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices,’ published 17 December 2025, supersedes the 2017 guidance that established the baseline framework. The critical change is the removal of the expectation that sponsors must always secure access to identifiable individual-level patient data. Previously, using large healthcare databases — national cancer registries, insurance claims databases, electronic health record networks — in a regulatory submission required the ability to provide individual patient records upon FDA request, a requirement that rendered many of the most valuable data sources — restricted to de-identified or aggregate access for privacy and HIPAA compliance reasons — unusable for regulatory purposes. The 2025 guidance lifts that barrier, opening large de-identified datasets containing millions of patient records to regulatory use, provided sponsors can demonstrate that the data are relevant, reliable, and fit for their intended purpose.
Since 2016, RWE has supported more than 250 medical device authorisations and over 35 drug and biologic applications. The December 2025 guidance formalises and expands this practice, with a new set of 73 examples of marketing authorisations using RWE from fiscal years 2020 to 2025 published to guide sponsors. Critically, the FDA’s press release explicitly stated that it intends to consider making equivalent changes to RWE guidance for drugs and biologics, signalling a broader policy direction that pharmaceutical companies should begin preparing for now.
The RWD Ecosystem: Wearables, EHRs, and Registries
The practical value of the expanded RWE framework depends on the quality and breadth of the real-world data ecosystem. Several components of this ecosystem have matured significantly in the past three to five years. Electronic health records, now near-universal in American and European hospital systems, contain longitudinal patient data — diagnoses, procedures, prescriptions, laboratory results, imaging — that can be systematically analysed to detect treatment effects, safety signals, and population-level disease patterns that no clinical trial could afford to study. Disease registries — for cancer, rare diseases, cardiovascular conditions, and others — have been collecting structured patient data for decades, accumulating sample sizes and follow-up durations that dwarf any single trial.
The newest and most dynamic component is digital health technology and wearables. Consumer devices — Apple Watch, continuous glucose monitors, pulse oximeters — and clinical-grade remote monitoring devices are generating continuous, granular physiological data from patients living their ordinary lives, rather than the episodic snapshots of clinical visits or the artificial conditions of a trial protocol. The FDA has explicitly recognised patient-generated data from wearables and digital health technologies as a legitimate RWD source under the new guidance. For certain indications — chronic disease management, cardiac monitoring, functional performance in elderly patients — wearable-generated endpoints may be more clinically relevant than the surrogate endpoints traditionally used in trials.
Compressing Clinical Timelines
The most consequential near-term implication of the expanding RWE framework is the potential to compress pharmaceutical development timelines — particularly for expanded indications, paediatric applications, and rare disease evidence generation. An approved drug seeking a new indication in a patient population too small to support a conventional randomised trial can increasingly be supported by structured RWE from registries and electronic health records, validated against existing safety and efficacy data. For rare diseases, where traditional trial enrolment is extraordinarily difficult and the patient populations too small to power standard statistical analyses, RWE may represent the only feasible path to regulatory evidence.
For India, the RWE transition carries particular strategic importance. India’s healthcare system generates enormous volumes of clinical data through its network of public hospitals, national health programmes, and AYUSH providers — data that has historically been siloed, poorly structured, and unavailable for systematic analysis. The Ayushman Bharat Digital Mission’s push toward Health ID interoperability and electronic health records represents the infrastructure investment required to make India’s clinical experience an asset in the global RWE ecosystem. Indian pharmaceutical companies with robust data partnerships and digital health capabilities could, within five years, be in a position to generate RWE datasets that support both regulatory submissions in India and potentially in international jurisdictions as the global regulatory harmonisation of RWE standards proceeds through the International Council for Harmonisation.
-Kalyan srinivas
